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Design, Synthesis, and Anti-Hepatocellular Carcinoma Evaluation Revealed by Transcriptome Analysis of Epimeric Sesquiterpene Lactones: Trilobolide-6-O-isobutyrate Analogues

  • 0Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou 571126, Hainan, People's Republic of China.
Journal of Natural Products +

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July 18, 2025

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July 18, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers synthesized 18 sesquiterpene lactone derivatives to treat hepatocellular carcinoma (HCC). Compounds 11 and 18 showed significant anti-cancer effects by inducing apoptosis and inhibiting cell growth, making them promising HCC treatment candidates.

Area Of Science

  • Medicinal Chemistry
  • Organic Synthesis
  • Cancer Biology

Background

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally.
  • Novel therapeutic strategies are urgently needed to combat HCC.
  • Sesquiterpene lactones are a class of natural products with potential anti-cancer properties.

Purpose Of The Study

  • To design and synthesize novel sesquiterpene lactone derivatives.
  • To evaluate the anti-cancer activity of these derivatives against HCC cell lines.
  • To investigate the mechanisms underlying their anti-tumor effects.

Main Methods

  • Synthesis of 18 sesquiterpene lactone derivatives (7 mustard derivatives, 11 amine adducts).
  • Structural characterization using NMR, HRESIMS, and X-ray crystallography.
  • In vitro anti-cancer activity assessment using CCK8 assays, cell apoptosis, cell cycle, proliferation, and migration assays.
  • Transcriptome analysis and ADME/physicochemical property prediction.

Main Results

  • Compounds 11 and 18 demonstrated potent inhibitory activity against HepG2 and Huh7 HCC cell lines.
  • Both compounds induced cell apoptosis, cell cycle arrest, and inhibited proliferation and migration.
  • Compound 18 showed potential antitumor effects via transcriptome analysis.
  • Compounds 11 and 18 exhibited favorable predicted ADME and physicochemical properties.

Conclusions

  • Sesquiterpene lactone derivatives 11 and 18 show significant promise as novel therapeutic agents for hepatocellular carcinoma.
  • Further investigation into these compounds could lead to the development of new HCC treatments.